Lessons learned from human HIV vaccine trials

The ability to induce broadly neutralizing antibody (bNAb) responses is likely essential for development of a globally effective HIV vaccine. Unfortunately, human vaccine trials conducted to date have failed to elicit broad plasma neutralization of primary virus isolates. Despite this limitation, in-depth analysis of the vaccine-induced memory B-cell repertoire can provide valuable insights into the presence and function of subdominant B-cell responses, and identify initiation of antibody lineages that may be on a path towards development of neutralization breadth.

Characterization of the functional capabilities of monoclonal antibodies isolated from a HIV-1 vaccine trial with modest efficacy has revealed mechanisms by which non-neutralizing antibodies are presumed to have mediated protection. In addition, B-cell repertoire analysis has demonstrated that vaccine boosts shifted the HIV-specific B-cell repertoire, expanding pools of cells with long third heavy chain complementarity determining regions - a characteristic of some bNAb lineages.

Detailed analysis of memory B-cell repertoires and evaluating the effector functions of isolated monoclonal antibodies expands what we can learn from human vaccine trails, and may provide knowledge that can enable rational design of novel approaches to drive maturation of subdominant disfavored bNAb lineages.